MM-398 (nanoliposomal irinotecan): emergence of a novel therapy for the treatment of advanced pancreatic cancer
MM-398 (nanoliposomal irinotecan): emergence of a novel therapy for the treatment of advanced pancreatic cancer
复制标题
DOI：
10.2217/fon.15.333
复制
发表时间：
2016-01-01
期刊：
影响因子：
3.3
通讯作者：
Ko, Andrew H.
中科院分区：
文献类型：
--
作者：
Carnevale, Julia;Ko, Andrew H.
虽然近年来晚期胰腺癌的治疗进展加快，但这种恶性肿瘤的预后仍然非常差，除了一线化疗之外没有标准的治疗选择。目前，有许多新的治疗药物处于临床开发的不同阶段，包括分子靶向药物、免疫疗法和细胞毒素的修饰版本。MM-398是一种新型的伊立替康纳米脂质体制剂，由于其良好的药代动力学特征，其设计目的是最大化肿瘤暴露，同时最小化全身毒性。总的来说，在多种疾病适应症的多项临床试验中，与标准伊立替康相比，MM-398已被证明具有良好的安全性和耐受性。最近在吉西他滨化疗难治性转移性胰腺癌患者中进行的III期NAPOLI-1试验结果显示，与单独使用5-氟尿嘧啶/亚叶酸钙相比，MM-398联合使用5-氟尿嘧啶/亚叶酸钙可显著提高总生存率。本文将重点介绍MM-398的开发和药代动力学特性，然后评估其安全性和有效性，重点介绍晚期胰腺癌的临床试验。
While progress in the treatment of advanced pancreatic cancer has accelerated in recent years, this malignancy continues to have an exceedingly poor prognosis, with no standard of care options beyond front-line chemotherapy. Currently, there are a number of new therapeutic agents in varying stages of clinical development, including molecularly targeted agents, immunotherapies, and modified versions of cytotoxics. MM-398, a novel nanoliposomal formulation of irinotecan, was designed to maximize tumor exposure while minimizing systemic toxicity due to its favorable pharmacokinetic profile. Overall, across multiple clinical trials in multiple disease indications, MM-398 has been shown to have a favorable safety and tolerability profile compared with standard irinotecan. Recent results of the Phase III NAPOLI-1 trial in patients with metastatic pancreatic cancer refractory to gemcitabine-based chemotherapy have shown a significant improvement in overall survival of MM-398 when combined with 5-fluorouracil/leucovorin, compared with 5-fluorouracil/leucovorin alone. This review focuses on the development and pharmacokinetic properties of MM-398, followed by evaluation of its safety and efficacy with a primary emphasis on clinical trials in advanced pancreatic cancer.